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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
MeSH Review

Methylation

 
 
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Disease relevance of Methylation

 

Psychiatry related information on Methylation

 

High impact information on Methylation

  • Large-genome eukaryotes use heritable cytosine methylation to silence promoters, especially those associated with transposons and imprinted genes [11].
  • Two methyltransferases from archaebacteria that catalyze methylation of mercaptoethanesulfonate (coenzyme M) during methanogenesis have also been shown to contain histidine-ligated cobamides [12].
  • Thymidylate synthase (TS, EC 2.1.1.45) catalyzes the reductive methylation of dUMP by CH2H4folate to produce dTMP and H2folate [13].
  • Carnitine biosynthesis is initiated by methylation of lysine [14].
  • We show that a paternally derived targeted deletion of the germline differentially methylated region (DMR) associated with the antisense Nespas transcript unexpectedly affects both the expression of all transcripts in the cluster and methylation of two DMRs [15].
 

Chemical compound and disease context of Methylation

 

Biological context of Methylation

  • Cytosine methylation does not reinforce or replace ancestral gene regulation pathways but instead endows methylated genomes with the ability to repress specific promoters in a manner that is buffered against changes in the internal and external environment [11].
  • Histone lysine methylation is a key regulator of gene expression and heterochromatin function, but little is known as to how this modification impinges on other chromatin activities [21].
  • NoRC mediates rDNA silencing by recruiting DNA methyltransferase and histone deacetylase activity to the rDNA promoter, thus establishing structural characteristics of heterochromatin such as DNA methylation, histone hypoacetylation and methylation of the Lys9 residue of histone H3 [22].
  • In Sp1-/- embryos, the expression of many putative target genes, including cell cycle-regulated genes, is not affected, CpG islands remain methylation free, and active chromatin is formed at the globin loci [23].
  • These results indicate an activator-based mechanism for joint MLL1 and MOF recruitment and targeted methylation and acetylation and provide a molecular explanation for the closely correlated distribution of H3 K4 methylation and H4 K16 acetylation on active genes [24].
 

Anatomical context of Methylation

  • We now show that the pattern of differential methylation in the 5' portion of H19 is established in the gametes and a subset is maintained in the pre-implantation embryo [25].
  • We report that CpG island methylation, an epigenetic modification of DNA known to correlate closely with silencing of gene transcription, appears in the oestrogen receptor (ER) gene in a subpopulation of cells which increases as a direct function of age in human colonic mucosa [26].
  • Although genomic methylation patterns were established normally in Dnmt1o-deficient oocytes, embryos derived from such oocytes showed a loss of allele-specific expression and methylation at certain imprinted loci [27].
  • Here we show that in the affected individual, in a transgenic model and in differentiating embryonic stem cells, transcription of antisense RNA mediates silencing and methylation of the associated CpG island [28].
  • We conclude that methylation at Hpa II sites is replicated by these cultured cells but not with 100% fidelity [29].
 

Associations of Methylation with chemical compounds

 

Gene context of Methylation

 

Analytical, diagnostic and therapeutic context of Methylation

References

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  19. Soybean GH3 promoter contains multiple auxin-inducible elements. Liu, Z.B., Ulmasov, T., Shi, X., Hagen, G., Guilfoyle, T.J. Plant Cell (1994) [Pubmed]
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  21. Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage. Sanders, S.L., Portoso, M., Mata, J., Bähler, J., Allshire, R.C., Kouzarides, T. Cell (2004) [Pubmed]
  22. The nucleolar remodeling complex NoRC mediates heterochromatin formation and silencing of ribosomal gene transcription. Santoro, R., Li, J., Grummt, I. Nat. Genet. (2002) [Pubmed]
  23. Transcription factor Sp1 is essential for early embryonic development but dispensable for cell growth and differentiation. Marin, M., Karis, A., Visser, P., Grosveld, F., Philipsen, S. Cell (1997) [Pubmed]
  24. Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF. Dou, Y., Milne, T.A., Tackett, A.J., Smith, E.R., Fukuda, A., Wysocka, J., Allis, C.D., Chait, B.T., Hess, J.L., Roeder, R.G. Cell (2005) [Pubmed]
  25. A paternal-specific methylation imprint marks the alleles of the mouse H19 gene. Tremblay, K.D., Saam, J.R., Ingram, R.S., Tilghman, S.M., Bartolomei, M.S. Nat. Genet. (1995) [Pubmed]
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  29. The somatic replication of DNA methylation. Wigler, M., Levy, D., Perucho, M. Cell (1981) [Pubmed]
  30. Solution structure of the methyl-CpG binding domain of human MBD1 in complex with methylated DNA. Ohki, I., Shimotake, N., Fujita, N., Jee, J., Ikegami, T., Nakao, M., Shirakawa, M. Cell (2001) [Pubmed]
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